This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (X65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m À2 two times daily on days 1 -14 every 3 weeks or S-1 40 -60 mg two times daily according to body surface area on days 1 -28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N ¼ 46) or S-1 (N ¼ 45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1 -40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6 -42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3 -4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3 -4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand -foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC.

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Summary:The current study defines the incidence and clinical manifestations of hyperacute graft-versus-host disease (haGVHD; fever, skin rash, diarrhea, and hepatic dysfunction) and analyzes the risk factor and the impact of haGVHD on the results of allogeneic stem cell transplantation (SCT). In all, 90 patients underwent allogeneic SCT from 71 matched siblings or 19 alternative donors. Immediate high-dose steroids were administered to 22 patients who met the criteria. The overall incidence of haGVHD was 36.7% (n ¼ 34) and haGVHD was also strongly correlated with acute (aGVHD) (Po0.001) and extensive chronic GVHD (cGVHD) (P ¼ 0.007), and found to be associated with decreased probability of relapse (P ¼ 0.0017). Early intervention with steroids within 7 days after the diagnosis of haGVHD might be associated with better survival. A survival analysis of the overall survival and disease-free survival did not reveal any difference between haGVHD þ and haGVHDÀ groups. In multivariate analysis, the use of an alternative donor (P ¼ 0.020) was identified as the only risk factor. Immediate high-dose steroids were effective in treating haGVHD. We conclude that in an allogeneic setting, haGVHD is not an uncommon manifestation, associated with the development of aGVHD or cGVHD. The only risk factor for haGVHD was the use of an alternative donor.

Summary:The impact of the CD34+ cell dose on chronic graftversus-host disease (cGVHD) and the clinical outcome was analyzed in 41 consecutive adult patients submitted to allogeneic peripheral blood stem cell transplantation from HLA-identical siblings. The patients were classified into 'low' or 'high' CD34+ cell dose groups based on whether they received less or more than a median CD34+ cell dose of 10.5 Â 10 6 /kg, respectively. There was a significant difference in the incidence of extensive cGVHD (low vs high group, 25.0 vs 66.7%, P ¼ 0.021) and relapse (47.6 vs 20.0%, P ¼ 0.049) between the two groups. With a median follow-up of 335 days, the 3-year survival estimate for the whole population was 47.9%, while that for the low and high groups was 29.9 and 67.8%, respectively (P ¼ 0.0434). An inverse relation was noted between the relapse rate and the incidence of extensive cGVHD (P ¼ 0.043). It would appear reasonable that the optimal dose of CD34+ cells should be determined based on the disease status or aggressiveness of the malignant cells in each patient. Yet, in the case of patients with a high risk of relapse, transplantation with a CD34+ cell dose of 410.5 Â 10 6 /kg would seem to be acceptable to minimize the risk of relapse. Bone Marrow Transplantation (2003) 31, 967-972.

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We aimed to evaluate the efficacy and safety of concurrent chemoradiotherapy with capecitabine and cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In total, 37 patients with stage III or IV SCCHN were enrolled on the study. The chemotherapy consisted of two cycles of intravenous cisplatin of 80 mg m À2 on day 1 and oral capecitabine 825 mg m À2 twice daily from day 1 to day 14 at 3-week intervals. The radiotherapy (1.8 -2.0 Gy 1 fraction day À1 to a total dose of 70 -70.2 Gy) was delivered to the primary tumour site and neck. The primary tumour sites were as follows: oral cavity (n ¼ 6), oropharynx (n ¼ 11), hypopharynx (n ¼ 8), larynx (n ¼ 3), nasopharynx (n ¼ 6), and paranasal sinus (n ¼ 3). After the chemoradiotherapy, 29 complete responses (78.4%) and 6 partial responses (16.2%) were confirmed. Grade 3 or 4 neutropenia occurred only in two patients, plus grade 3 febrile neutropenia was observed only in one patient. At a median follow-up duration of 19.8 months, the estimated overall survival and progression-free survival rate at 2-year was 76.8 and 57.9%, respectively. Concurrent chemoradiotherapy with capecitabine and cisplatin was found to be well tolerated and effective in patients with locally advanced SCCHN.

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Bone loss is recognized as worsening the quality of life in long-term survivors of Allo-SCT. This study evaluated the risk factors associated with bone loss and the role of zoledronic acid in preventing bone loss in allogeneic recipients. Fifty-three patients who underwent HLAmatched Allo-SCT were evaluated for their bone mineral density (BMD) in the lumbar spine and femoral neck at regular intervals. Zoledronic acid (4 mg) was given i.v. to 18 patients (ZA patients) at 2 months after SCT and then every 3 months until 2 years. Grade 2-4 acute GVHD was associated with bone loss (odds ratio (OR) ¼ 4.90, 95% confidence interval (CI) ¼ 1.41-16.99; P ¼ 0.012) at 1 year after SCT, whereas extensive chronic GVHD and steroid use were both unfavorable prognostic factors (OR ¼ 9.00 and 7.22, 95% CI ¼ 1.52-53.40 and 1.44-36.22; P ¼ 0.016, respectively) in terms of osteopenia/ osteoporosis at 2 years after transplantation. The use of zoledronic acid significantly prevented bone loss in the femoral neck as well as the spine (OR ¼ 0.18, 95% CI ¼ 0.05-0.69, P ¼ 0.012). Therefore, BMD measurements and the use of zoledronic acid are recommended in cases of GVHD or long-term steroid use after Allo-SCT to prevent bone loss and threatening skeletal events.